Evidence that testosterone modulates in vivo the adenylate cyclase activity in fat cells.
In male hamster fat cell membranes, the alpha 2-adrenoreceptor-mediated inhibitory response of adenylate cyclase was almost completely suppressed by castration and was restored to control values after testosterone treatment, whereas the cyclase inhibitory response to nicotinic acid was insensitive to androgenic status. Basal and forskolin-, guanylylimidodiphosphate- and isoproterenol-stimulated cyclase activities were decreased by 30-40% after castration and restored to control values after testosterone treatment. In addition, Mn2+ + forskolin-stimulated activity in the presence or absence of GDP beta S was lower (-30%) after castration and normalized after testosterone treatment. Finally, the effects of testosterone described above were completely abolished when the potent androgen receptor antagonist RU 23908 was administered together with testosterone. These results indicate that both the inhibitory and stimulatory responses of adenylate cyclase are promoted by testosterone through an androgen receptor-dependent mechanism; promotion of the inhibitory response concerns specifically the alpha 2-receptor-mediated pathway, whereas promotion of the stimulatory response appears unspecific and mainly due to increased activity of the cyclase catalytic subunit.
Pecquery
R
R
Department of Biochemistry, Faculty of Medicine Paris-Ouest, Centre Hospitalier de Poissy, France.
Dieudonne
M N
MN
Leneveu
M C
MC
Giudicelli
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000726:Androgen Antagonists; D007093:Imidazoles; D048289:Imidazolidines; D013739:Testosterone; C021277:nilutamide; D000262:Adenylyl Cyclases